Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine

IF 5 2区医学 Q1 CLINICAL NEUROLOGY

Bipolar Disorders Pub Date : 2024-04-01 DOI:10.1111/bdi.13423

Roger B. Varela, Suelen L. Boschen, Nathanael Yates, Tristan Houghton, Charles D. Blaha, Kendall H. Lee, Kevin E. Bennet, Abbas Z. Kouzani, Michael Berk, João Quevedo, Samira S. Valvassori, Susannah J. Tye

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Abstract

Background

Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD.

Aim

The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph).

Methods

Wistar rats were given 14 days of m-amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low-frequency stimulation (LFS) or continuous high-frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field tests and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry.

Results

M-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M-amph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc.

Conclusion

These results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.

Abstract Image

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在由甲基苯丙胺诱发的躁狂症动物模型中，对腹侧被盖区进行深部脑刺激的抗躁狂效果。

背景：难治性双相情感障碍（BD）的治疗极具挑战性。脑深部刺激（DBS）有望成为一种有效的治疗干预手段。目的：本研究旨在探讨腹侧被盖区（VTA）DBS在甲基苯丙胺（m-amph）诱导的躁狂症动物模型中的行为和神经化学效应：对Wistar大鼠注射甲基苯丙胺（m-amph）14天，最后一天对动物进行20分钟的VTA DBS，有两种不同的模式：间歇性低频刺激（LFS）或连续性高频刺激（HFS）。DBS后，立即通过开阔地测试和快速扫描循环伏安法评估了不同组动物的躁狂样行为和伏隔核（NAc）相性多巴胺（DA）释放情况。免疫组化法评估了NAc多巴胺能标记物的水平：结果：M-amph能诱导动物过度运动，而两种DBS参数都能逆转这种改变。与基线水平相比，M-amph增加了sham后的DA再摄取时间，而LFS和HFS都能阻断这种改变。与基线相比，LFS 还能减少阶段性 DA 释放。LFS 能够增加 NAc 中多巴胺转运体（DAT）的表达：这些结果表明，VTA LFS 和 HFS DBS 都具有抗躁狂作用，并能调节 NAc 中的 DA 动态。更具体地说，DAT表达增加导致的DA再摄取增加可能是VTA DBS发挥抗躁狂作用的潜在机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bipolar Disorders 医学-精神病学

CiteScore

8.20

自引率

7.40%

发文量

审稿时长

6-12 weeks

期刊介绍： Bipolar Disorders is an international journal that publishes all research of relevance for the basic mechanisms, clinical aspects, or treatment of bipolar disorders and related illnesses. It intends to provide a single international outlet for new research in this area and covers research in the following areas: biochemistry physiology neuropsychopharmacology neuroanatomy neuropathology genetics brain imaging epidemiology phenomenology clinical aspects and therapeutics of bipolar disorders Bipolar Disorders also contains papers that form the development of new therapeutic strategies for these disorders as well as papers on the topics of schizoaffective disorders, and depressive disorders as these can be cyclic disorders with areas of overlap with bipolar disorders. The journal will consider for publication submissions within the domain of: Perspectives, Research Articles, Correspondence, Clinical Corner, and Reflections. Within these there are a number of types of articles: invited editorials, debates, review articles, original articles, commentaries, letters to the editors, clinical conundrums, clinical curiosities, clinical care, and musings.